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Biomedical subjects

F L Pearce

Publications and source records attributed to F L Pearce.

At least 127 records · Page 7Linked to original sources
PubMed1982

A comparative study of histamine secretion from rat peritoneal and pleural mast cells.

The effects of various histamine liberators and inhibitors on isolated rat peritoneal and pleural mast cells have been compared. The pleural cells showed an increased reactivity to challenge with antigen following passive, but not active, sensitization and were more responsive to challenge with anti-IgE. Phosphatidyl serine enhanced the secretion from both cell types. Peritoneal and pleural cells exhibited virtually identical responses after treatment with chemical secretagogues in the presence of exogenous calcium, but the peritoneal cells were significantly more reactive to stimulation with basic inducers in the absence of the cation. Anaphylactic histamine secretion was comparably inhibited by a number of anti-allergic drugs but the peritoneal cells were rather more sensitive to inhibition by dibutyryl cyclic AMP. These results are discussed in terms of the general functional heterogeneity of mast cells from different sources.

Anaphylaxis↗
PubMed1982

Effect of ketotifen and oxatomide on histamine secretion from mast cells.

The anti-histaminic drugs ketotifen and oxatomide have a dual effect on rat peritoneal mast cells. At high concentrations they induce histamine release, whereas at low concentrations they inhibit secretion evoked by IgE-directed ligands. The latter effect is observed in the presence and absence of exogenous calcium. The significance of this result for the general mode of action of anti-anaphylactic drugs is discussed. Neither compound liberates histamine from isolated mesenteric cells from the rat or guinea pig, further emphasizing the functional heterogeneity of mast cells from different sources.

Animals↗
PubMed1982

Phosphatidic acid induces histamine secretion from rat peritoneal mast cells.

Phosphatidic acid produces a selective, dose-dependent release of histamine from rat peritoneal mast cells. The effect is independent of exogenous calcium and probably reflects mobilization of sequestered stores of the cation. The significance of these results is discussed in terms of the possible changes in membrane lipid metabolism involved in mast cell activation.

Animals↗
PubMed1982

Some characteristics of histamine secretion from mast cells treated with ionomycin.

The ionophorous antibiotic ionomycin released histamine from rat peritoneal mast cells in both the presence and absence of added calcium ions. The response under the latter conditions was potentiated by brief pretreatment of the cells with chelating agents. The interaction between the ionophore and exogenous calcium was complex. Supramaximal concentrations of calcium potentiated the release induced by low levels of ionomycin but markedly inhibited the secretion evoked by larger amounts of the compound. Dispersed mesenteric mast cells of the rat and guinea pig also responded to ionomycin but were less reactive than the peritoneal cells.

Animals↗
PubMed1982

Mucosal mast cells. I. Isolation and functional characteristics of rat intestinal mast cells.

We have developed a procedure for the dispersion of mast cells from the intestinal lamina propria (LP) and epithelium of rats infected with the intestinal nematode, Nippostrongylus brasiliensis. The dispersed cells are morphologically and histochemically similar to intestinal mucosal mast cells (MMC) in situ and are distinguishable from peritoneal mast cells (PMC). MMC derived from the LP or epithelium of parasitized animals secrete histamine in response to the specific parasite antigens as well as anti-IgE. Unlike PMC, these cells are unresponsive to the basic secretagogues 48/80 and bee venom peptide 401. Similarly, bee venom peptide 401 conjugated with dansyl chloride binds to PMC and mast cells in the thymus and intestinal serosa, but not to mast cells in or derived from the intestinal LP and epithelium. Studies on PMC treated by the intestinal cell isolation procedure show that the functional characteristics of the MMC cannot be solely attributed to the isolation procedure. Thus, MMC have been isolated and shown to be morphologically, histochemically, and functionally different from PMC, as suggested by previous in vivo studies of the normal intestine.

Animals↗
PubMed1982

Mucosal mast cells. II. Effects of anti-allergic compounds on histamine secretion by isolated intestinal mast cells.

Functional mast cells have been isolated from the lamina propria of the small intestine of rats infected with the nematode Nippostrongylus brasiliensis. The cells released histamine on challenge with specific antigen, anti-rat IgE, concanavalin A, and calcium ionophores but were less responsive than peritoneal mast cells (MMC) from the same animals. Intestinal mucosa mast cells (PMC) were refractory to the action of the basic secretagogues peptide 401 from bee venom and compound 48/80. The anti-allergic compounds disodium cromoglycate (less than or equal to 10(-3) M), AH 9679 (less than or equal to 10(-4) M), and theophylline (less than or equal to 10(-2)) did not inhibit antigen-induced histamine secretion by MMC, although these compounds were effective against PMC. In contrast, doxantrazole (10(-5) to 10(-3) M) inhibited the secretion of histamine from both MMC and PMC in a comparable dose-dependent fashion. Thus, we have established that mast cells from different sites are functionally heterogeneous not only in their response to various stimuli for histamine secretion, but also in their responses to different pharmacologic modulators of secretion. It cannot be assumed that anti-allergic compounds effective against mast cells in one tissue site or organ will be equally efficacious against mast cells in other sites. The extent of this functional heterogeneity must be established, and its investigation may provide new insights into the biochemical events involved in mast cell secretion.

Animals↗
PubMed1982

Characteristics of histamine secretion from rat peritoneal mast cells sensitized to the nematode Nippostrongylus brasiliensis.

Peritoneal mast cells from rats immunized with the nematode Nippostrongylus brasiliensis released histamine on challenge with antigen in both the presence and absence of added calcium. The response under the latter conditions was abolished by depletion of sequestered stores of the cation and probably reflected mobilization of these stores. The release was potentiated by brief pretreatment with chelating agents and inhibited (in the absence of phosphatidyl serine, PS) by supramaximal concentrations of calcium. Calcium bound to superficial sites in the membrane may then regulate the secretory process. Histamine release in both the presence and absence of calcium was enhanced by adenosine. Only the former response was potentiated by PS, in keeping with the view that the lipid promotes influx of the cation from the extracellular environment. The activated state induced by antigen decayed with time but PS slowed this process. Histamine secretion in the absence of calcium was more rapid than in the presence of the cation, consistent with the release of bound calcium in a pulse of short duration.

Adenosine↗
PubMed1982

Effect of anti-allergic compounds on anaphylactic histamine secretion from rat peritoneal mast cells in the presence and absence of exogenous calcium.

The anti-allergic drugs theophylline, doxantrazole, quercetin, 8-bromo cyclic AMP, and disodium cromoglycate prevented anaphylactic histamine release from rat peritoneal mast cells in both the presence and absence of extracellular calcium. The activity of the test compounds under the latter conditions cannot be simply explained in terms of their postulated ability to block movement of the cation from the external environment into the cell. Alternative modes of action are thus considered.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1981

Inhibition of histamine secretion from mast cells.

Histamine secretion from mast cells may be inhibited by elevated intracellular levels of cyclic AMP and by several anti-allergic drugs. These compounds are claimed to act directly on the calcium-gating mechanism activated by the anaphylactic reaction, preventing influx of Ca2+ from the external environment and so blocking exocytosis. To examine this hypothesis further, we have compared here the histamine secretion induced by immunoglobulin E-directed ligands in the presence and absence of added calcium and by the ionophore A23187. Exocytosis evoked by these former agents was originally considered to be almost totally dependent on extracellular calcium but recent studies have shown otherwise. In the absence of added cation, the agents act by mobilizing membrane-bound or intracellular stores of calcium. We show that here that a variety of anti-allergic drugs are potent inhibitors in the conditions used, suggesting that alternative explanations for their action must be sought.

Animals↗
PubMed1981

Role of membrane bound calcium in histamine secretion from rat peritoneal mast cells.

Calcium loosely bound to the mast cell membrane may be utilized for histamine release induced by antigen, concanavalin A, compound 48/80 and the calcium ionophore A23187. Cells incubated in the presence of calcium and diluted into a medium free of divalent cations give a maximal release of histamine which decays with time, consistent with dissociation of the ion from the membrane. Anti-rat IgE and suboptimal concentrations of the ionophore show an immediate decrease in response followed by a further progressive decay. These results are consistent with the slower progress decay. These results are consistent with the slower time-course of secretion shown by these agonists, thus permitting dissociation of calcium from the membrane, before exocytosis is induced. In accord with this hypothesis, the initial suppression of response to the ionophore is reversed by preincubation of the cells with adenosine which enhances the rate of histamine release. The response of dextran is totally abolished by the described treatment, supporting suggesting that free extracellular calcium may be required for the polysaccharide to express its activity.

Adenosine↗
PubMed1981

Role of intra- and extracellular calcium in histamine release from rat peritoneal mast cells.

The present study provides evidence for a number of calcium pools important in histamine secretion from the mast cell. Firstly, calcium loosely bound to the cell membrane, and in rapid equilibrium with the extracellular environment, may be utilized for histamine release induced by most secretagogues. Secondly, all inducers are able to mobilize deeply buried or internal stores of calcium to initiate exocytosis. Finally, calcium bound to regulatory sites in the membrane may modulate the secretory process. Removal of calcium from the latter sites by brief treatment with chelating agents markedly enhances the secretory response in the absence of extracellular calcium, probably by facilitating the mobilization of bound stores of the ion. Saturation of these sites in the presence of excess calcium inhibits the release process and may restrict influx of the cation.

Animals↗
PubMed1981

Effect of lanthanide ions on histamine secretion from rat peritoneal mast cells.

1 Ions of the lanthanide series (lanthanum-lutetium) inhibit histamine release induced by allergen and anti-IgE in the presence of extracellular calcium. The inhibition is dose-dependent in the range 10(-6) to 10(-9) M and there is no marked difference in potency between the lanthanides. 2 The response to lanthanum is biphasic and higher concentrations (10(-4) M) potentiate the release. Maximal concentrations (10(-3) M) again abolish secretion. 3 The effect of concanavalin A is weakly antagonized by lanthanum but strongly inhibited by higher lanthanides. 4 Inhibition of histamine release evoked by basic agents is markedly dependent on the ionic radius of the lanthanide. In the presence of extracellular calcium, dysprosium is the most effective inhibitor. Similar results are observed with dextran. In the absence of calcium, there is a regular increase in inhibition with decreasing ionic radius. 5 Inhibition of release in the presence of calcium is immediate and does not require preincubation with the lanthanide. The antagonism due to lanthanum is competitive and the pA2 values vary with the secretagogue. In contrast, the inhibitory effect in the absence of extracellular calcium increase progressively with time. 6 These results are discussed in terms of the calcium-pools important in histamine release and the mode of action of different secretagogues.

Animals↗